HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen.

Allogeneic blood or marrow transplantation (BMT) is a curative therapy for chronic myeloid leukemia (CML). We have previously reported that the pharmacologic targeting of busulfan combined with cyclophosphamide (TBU/CY) can minimize regimen-related toxicity while preserving antileukemic effects. We report here on 131 consecutive chronic-phase CML patients treated with allogeneic related BMT using a TBU/CY preparative regimen, where the busulfan dose was targeted to achieve a steady-state plasma concentration of at least 900 ng/mL. The median age of the patients was 43 years (range, 14-66 years). Estimates of the probabilities of nonrelapse mortality, relapse, survival, and disease-free survival 3 years after transplantation were 14%, 8%, 86%, and 78%, respectively. Age had no statistically significant effect on survival. Although approximately 60% of the patients developed clinically extensive chronic graft-versus-host disease, the median Karnofsky score at last contact date among survivors was 95%. Of surviving patients, 11% were molecularly positive for the bcr-abl mRNA at last contact, with a median level of bcr-abl transcripts of 4.6 copies/microg RNA. These data suggest that TBU/CY is a very effective preparative regimen for CML in chronic phase, associated with an expected survival at 3 years of approximately 85%, with most patients being in molecular remission.